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Schneider, Katja U; Dietrich, Dimo; Fleischhacker, Michael; Leschber, Gunda; Merk, Johannes; Schäper, Frank; Stapert, Henk R; Vossenaar, Erik R; Weickmann, Sabine; Liebenberg, Volker; Kneip, Christoph; Seegebarth, Anke; Erdogan, Fikret; Rappold, Gudrun; Schmidt, Bernd

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

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  • Media type: E-Article
  • Title: Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors
  • Contributor: Schneider, Katja U; Dietrich, Dimo; Fleischhacker, Michael; Leschber, Gunda; Merk, Johannes; Schäper, Frank; Stapert, Henk R; Vossenaar, Erik R; Weickmann, Sabine; Liebenberg, Volker; Kneip, Christoph; Seegebarth, Anke; Erdogan, Fikret; Rappold, Gudrun; Schmidt, Bernd
  • imprint: Springer Science and Business Media LLC, 2011
  • Published in: BMC Cancer
  • Language: English
  • DOI: 10.1186/1471-2407-11-102
  • ISSN: 1471-2407
  • Keywords: Cancer Research ; Genetics ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>DNA methylation in the <jats:italic>SHOX2</jats:italic> locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with <jats:italic>SHOX2</jats:italic> gene expression and/or copy number alterations. An amplification of the <jats:italic>SHOX2</jats:italic> gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p> <jats:italic>SHOX2</jats:italic> expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect <jats:italic>SHOX2</jats:italic> DNA methylation levels. <jats:italic>SHOX2</jats:italic> expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A hypermethylation of the <jats:italic>SHOX2</jats:italic> locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p &lt; 0.0001), while the expression of the <jats:italic>SHOX2</jats:italic> gene showed no difference.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Frequent gene amplification correlated with hypermethylation of the <jats:italic>SHOX2</jats:italic> gene locus. This concerted effect qualifies <jats:italic>SHOX2</jats:italic> DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.</jats:p> </jats:sec>
  • Access State: Open Access